Bremer S, Pellizzer C, Hoffmann S, Seidle T, Hartung T
European Centre for the Validation of Alternative Methods, Institute for Health and Consumer Protection, Joint Research Centre, European Commission, Via Fermi1, 21020 Ispra (VA), Italy.
Curr Pharm Des. 2007;13(29):3047-58. doi: 10.2174/138161207782110462.
Large scale toxicological testing programmes which are currently ongoing such as the new European chemical legislation REACH require the development of new integrated testing strategies rather than applying traditional testing schemes to thousands of chemicals. The current practice of requiring in vivo testing for every possible adverse effect endanger the success of these programmes due (i) to limited testing facilities and sufficient capacity of scientific/technical knowledge for reproductive toxicity; (ii) an unacceptable number of laboratory animals involved (iii) an intolerable number of chemicals classified as false positive. A key aspect of the implementation of new testing strategies is the determination of prevalence of reproductive toxicity in the universe of industrial chemicals. Prevalences are relevant in order to be aware on the expected rate of false classification during the toxicological testing and to implement appropriate measures for their avoidance. Furthermore, a detailed understanding on the subendpoints affected by reproductive toxicants and the underlying mechanisms will lead to more science based testing strategies integrating alternative methods without compromising the protection of consumers.
目前正在进行的大规模毒理学测试项目，如新的欧洲化学品法规REACH，需要开发新的综合测试策略，而不是将传统测试方案应用于数千种化学品。当前对每种可能的不良反应都要求进行体内测试的做法危及这些项目的成功，原因如下：（i）生殖毒性的测试设施和科学/技术知识的足够能力有限；（ii）涉及的实验动物数量不可接受；（iii）被归类为假阳性的化学品数量令人无法容忍。新测试策略实施的一个关键方面是确定工业化学品领域中生殖毒性的发生率。发生率很重要，以便了解毒理学测试期间预期的错误分类率，并采取适当措施避免这些错误分类。此外，对受生殖毒物影响的子终点及其潜在机制的详细了解将导致更基于科学的测试策略，整合替代方法，同时又不损害对消费者的保护。
